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REPORT: Reaffirming the Role of Surgery in Pleural Mesothelioma Treatment

A Critical Response to the MARS 2 Trial

This report summarizes and contextualizes the article 'Going to MARS May Shorten Our Patient’s Survival,' published in The Journal of Thoracic and Cardiovascular Surgery (December 2024), which responds to the findings of the MARS 2 trial. The authors—internationally recognized thoracic surgeons and mesothelioma specialists—present a detailed critique of MARS 2 and reaffirm the vital role that surgery plays in treating pleural mesothelioma (PM) when integrated into a multimodal approach for properly selected patients. This rebuttal addresses concerns that MARS 2 may be misinterpreted as evidence to discontinue surgical intervention in PM care.

1. Background on MARS Trials

MARS 1:

Published in 2011 in The Lancet Oncology, MARS 1  was a feasibility study assessing the value of extrapleural pneumonectomy (EPP) in PM. EPP is a radical surgical procedure for PM that involves removal of the tumor along with the affected lung, adjacent pleura, diaphragm, and often part of the pericardium. The study concluded that EPP did not improve survival and may cause harm in some cases. With only 50 randomized patients, it raised significant doubts about EPP and led to increased interest in extended pleurectomy decortication (ePD), a less radical surgery for PM in which the tumor and pleura are removed while preserving the lung, as a safer alternative.

MARS 2:

Published in June 2024 in The Lancet Respiratory Medicine, MARS 2 was a larger phase 3 randomized clinical trial comparing ePD plus chemotherapy to chemotherapy alone in 335 patients. The trial found a median overall survival (OS) of 19.3 months in the surgery arm versus 24.8 months in the chemo-only arm and concluded that ePD offered no survival benefit. However, serious methodological flaws in the study have been identified by thoracic experts.

2. Purpose and Origin of the Rebuttal Article

The rebuttal article, 'Going to MARS May Shorten Our Patient’s Survival,' authored by 13 internationally recognized thoracic surgeons and mesothelioma experts across leading institutions in the U.S., Canada, and Europe, was published to counteract the potentially misleading conclusions of MARS 2. These experts include:

  • Dr. R. Taylor Ripley (Baylor College of Medicine)
  • Dr. Robert B. Cameron (UCLA)
  • Dr. Raphael Bueno (Harvard/Brigham and Women’s)
  • Dr. Raja Flores (Mount Sinai)
  • Dr. Harvey Pass (NYU)
  • Dr. Marc de Perrot (Toronto General/Princess Margaret)
  • and others representing centers that perform high-volume, specialized mesothelioma surgery.

These authors were compelled to respond due to concerns that non-surgical oncologists and policymakers might interpret MARS 2 as definitive proof against surgery, despite its serious methodological flaws. Their goal was to preserve access to life-extending surgical options for appropriately selected patients and ensure balanced interpretation of the evidence.

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